The deafwaddler (dfw) mouse is presently a model for recessive sensorineural deafness. Heterozygous mice, however, show variable hearing loss depending on the background and the severity of the dfw allele. The causative mutation affects the Atp2b2 gene encoding the plasma membrane calcium pump PMCA2 (Street, et al., 1998). The ultimate goal of the present study is to evaluate dfw heterozygotes as a model for age-related hearing loss (AHL) and noise-induced hearing loss (NIHL). A partial loss-of-function allele (dfw) and a functional null allele (dfw-J) will be used (Penheiter et al., 2001; Street et al., 1998). Both alleles are maintained in a CBA/CaJ background, the "gold standard" for hearing in mice. We will measure hearing loss using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. The organ of Corti will also be examined microscopically in order to correlate histopathology with functional measurements. An additional aim is to investigate a potential genetic interaction between the dfw and waltzer (v) loci by examining the susceptibility to NIHL in trans-heterozygotes.